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LCH-IV, Mezinárodní protokol kolaborativní léčby pro děti a dospívající s histiocytózou z Langerhansových buněk

9. listopadu 2026 aktualizováno: North American Consortium for Histiocytosis

The LCH-IV is an international, multicenter, prospective clinical study for pediatric Langerhans Cell Histiocytosis LCH (age < 18 years).

Přehled studie

Postavení

Aktivní, ne nábor

Podmínky

Intervence / Léčba

Detailní popis

The international efforts of the past 20 years have shown that combination therapy with vinblastine and prednisone is an effective therapy for Multi-system (MS)-LCH. The previous prospective trial LCH-III confirmed this regimen as a standard regimen for MS-LCH in patients with and without risk organ involvement. It also showed that prolonged treatment in the latter group (treatment duration of 12 vs. 6 months) is superior in preventing disease reactivations. The results of this trial are encouraging and serve as a basis for the LCH-IV study design.Due to the complexity of the disease presentations and outcomes, the LCH-IV study seeks to tailor treatment based on features at presentation and on response to treatment, leading to seven strata:

  • Stratum I: First-line treatment for MS-LCH patients (Group 1) and patients with Single system (SS)-LCH with multifocal bone or "Central Nervous System (CNS)-risk" lesions (Group 2)
  • Stratum II: Second-line treatment for non-risk patients (patients without risk organ involvement who fail first-line therapy or have a reactivation after completion of first-line therapy)
  • Stratum III: Salvage treatment for risk LCH (patients with dysfunction of risk organs who fail first-line therapy)
  • Stratum IV: Stem cell transplantation for risk LCH (patients with dysfunction of risk organs who fail first-line therapy)
  • Stratum V: Monitoring and treatment of isolated tumorous and neurodegenerative CNS-LCH
  • Stratum VI: Natural history and management of "other" SS-LCH (patients who do not need systemic therapy at the time of diagnosis)
  • Stratum VII: Long-term Follow up (all patients irrespective of previous therapy will be followed for reactivation or permanent consequences once complete disease resolution has been achieved and the respective protocol treatment completed)

Typ studie

Intervenční

Zápis (Aktuální)

1400

Fáze

  • Fáze 2
  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

    • Alabama
      • Birmingham, Alabama, Spojené státy, 35233
        • Children's of Alabama
    • Arizona
      • Phoenix, Arizona, Spojené státy, 85006
        • Phoenix Children's Hospital
    • Arkansas
      • Little Rock, Arkansas, Spojené státy, 72202
        • Arkansas Children's Hospital
    • California
      • Los Angeles, California, Spojené státy, 90027
        • Children's Hospital of Los Angeles
      • Madera, California, Spojené státy, 93636
        • Valley Children's Healthcare
      • Oakland, California, Spojené státy, 94609
        • UCSF Benioff Children's Hospital of Oakland
      • Orange, California, Spojené státy, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, Spojené státy, 94158-0106
        • UCSF Helen Diller Family Cancer Center
    • Connecticut
      • Hartford, Connecticut, Spojené státy, 06106
        • Connecticut Children's Medical Center
    • District of Columbia
      • Washington D.C., District of Columbia, Spojené státy, 20010
        • Children's National Medical Center
    • Florida
      • St. Petersburg, Florida, Spojené státy, 33701
        • Johns Hopkins All Children's Hospital
    • Georgia
      • Atlanta, Georgia, Spojené státy, 30342
        • Children's Healthcare of Atlanta, Emory
    • Illinois
      • Chicago, Illinois, Spojené státy, 60611-2991
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis, Indiana, Spojené státy, 46202
        • Riley Hospital for Children - Indiana University
    • Kansas
      • Kansas City, Kansas, Spojené státy, 64108
        • Children's Mercy Hospitals
    • Kentucky
      • Lexington, Kentucky, Spojené státy, 40536
        • University of Kentucky A.B.Chandler Medical Center
      • Louisville, Kentucky, Spojené státy, 40202
        • University of Louisville, Norton Children's Hospital
    • Maryland
      • Baltimore, Maryland, Spojené státy, 21287
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, Spojené státy, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, Spojené státy, 02115
        • Dana Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, Spojené státy, 55404
        • Children's Minnesota
    • New Jersey
      • Hackensack, New Jersey, Spojené státy, 07601
        • Hackensack University Medical Center
    • New York
      • New Hyde Park, New York, Spojené státy, 11040
        • Cohen Children's Medical Center
      • New York, New York, Spojené státy, 10029
        • Mount Sinai Hospital
      • New York, New York, Spojené státy, 10032
        • Columbia University / Herbert Irving Cancer Center
      • New York, New York, Spojené státy, 10170
        • Memorial Sloan Kettering Cancer Center
      • Syracuse, New York, Spojené státy, 13210
        • SUNY Upstate Medical University
      • The Bronx, New York, Spojené státy, 10467
        • Children's Hospital at Montefiore
    • North Carolina
      • Charlotte, North Carolina, Spojené státy, 28203
        • Carolinas Medical Center, Levine Children's Hospital
    • Ohio
      • Akron, Ohio, Spojené státy, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, Spojené státy, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, Spojené státy, 44106
        • Rainbow Babies & Children's Hospital, University Hospitals
      • Toledo, Ohio, Spojené státy, 43606
        • Russell J Ebeid Children's Hospital (Promedica)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Spojené státy, 15224
        • UPMC Children's Hospital of Pittsburgh
    • South Carolina
      • Charleston, South Carolina, Spojené státy, 29425
        • Medical University of South Carolina (MUSC)
      • Greenville, South Carolina, Spojené státy, 29605
        • Greenville Health System BI-LO Charities Children's Cancer Center
    • Tennessee
      • Memphis, Tennessee, Spojené státy, 38105
        • St. Jude Children's Research Hospital
      • Nashville, Tennessee, Spojené státy, 37232
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Dallas, Texas, Spojené státy, 75235
        • Children's Medical Center Dallas, UT Southwestern
    • Washington
      • Spokane, Washington, Spojené státy, 99204
        • Providence Sacred Heart Children's Hospital
      • Tacoma, Washington, Spojené státy, 98431
        • Madigan Army Medical Center
    • Wisconsin
      • Madison, Wisconsin, Spojené státy, 53792
        • American Family Children's Hospital University of Wisconsin

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

Ne starší než 18 let (Dítě, Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

Inclusion Criteria:

  • Stratum I

    • Patients must be less than 18 years of age at the time of diagnosis.
    • Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1
    • Signed informed consent form
  • Stratum II

    • Patients of Stratum I who have:
    • Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
    • AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2)
    • Disease progression (AD worse) in non-risk organs at any time during continuation treatment
    • Active disease at the end of Stratum I treatment
    • Disease reactivation in non-risk organs at any time after completion of Stratum I treatment
  • Stratum III

    • Patients from Stratum I who fulfill the following criteria:

    • AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2).

    • Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as

      • Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
      • PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR
      • Liver dysfunction (or digestive involvement with protein loss)
      • Total protein <55 g/L or substitution dependency
      • Albumin <25 g/L or substitution dependency (at least one of the two criteria to be fulfilled)
  • Stratum IV

    • Patients from Stratum I or Stratum III who fulfill the following criteria:
    • AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I OR
    • AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
    • Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as defined in Table XI (see Section 10.3.1).
    • Informed consent: All patients or their legal guardians (if the patient is <18 years of age) must sign an Ethics or institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study. When appropriate, younger patients will be included in all discussions in order to obtain assent.
    • Adequate organ function: Patients should have adequate hepatic, renal, cardiac and pulmonary function to undergo reduced intensity HCT based upon local institutional guidelines, or at a minimum meet requirements noted in eligibility checklist Appendix A-VIII_1. However, significant hepatic and pulmonary dysfunction, if secondary to underlying LCH disease activity, will not exclude patients from protocol enrollment and should be discussed with the National PI Coordinator and the Coordinating Principal Investigator.
  • Stratum V

    • All patients with verified diagnosis of LCH and MRI findings consistent with ND-CNSLCH irrespective of previous treatments (also those not registered to other Strata ofLCH-IV).
    • Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion in the hypothalamus-pituitary axis). In patients with already established diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion is needed for inclusion into the study
  • Stratum VI

    -- Patients with newly diagnosed SS-LCH and localization other than "multifocal bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.

  • Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as consent for longterm follow-up has not been withheld.

Exclusion Criteria:

  • Stratum I

    • Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy)
    • LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease
    • Prior systemic therapy
  • Stratum II

    • Patients with progressive disease in risk organs
    • Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations
    • No written consent of the patient or his/her parents or legal guardian
  • Stratum III

    • The presence of any of the following criteria will exclude the patient from the study:
    • Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement.
    • Inadequate renal function as defined by serum creatinine > 3x normal for age
  • Stratum IV

    • Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
    • Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
    • Uncontrolled active life-threatening infection.
    • Decreased renal function with a GFR of less than 50ml/1.73m2/min.
    • Pregnancy or active breast feeding
    • Failure to provide signed informed consent
  • Stratum VI

    • Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible for Stratum V),
    • Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible for Stratum I, Group 2)

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Stratum I

Stratum I The combination of Prednisone and vinblastine is the standard first-line combination for patients needing systemic therapy (Stratum I). Patients with MS-LCH and involvement of risk organs, who do not respond to 6-12 weeks of standard therapy, will be immediately switched to alternative treatment approaches (Stratum III or Stratum IV).

Further therapy prolongation (12 vs. 24 months) and intensification (± mercaptopurine) will further reduce the reactivation rate and the permanent consequences.

Stratum I

Stratum I

Ostatní jména:
  • Velban®
  • Vincaleukoblastin sulfát

Stratum I

Ostatní jména:
  • -Purinethol®
  • -6-MP
Experimentální: Stratum II

A uniform "intensive" 24-week course consisting of prednisolone, vincristine and cytosine-arabinoside will be introduced in Stratum II for eligible patients. It will be followed by a continuation therapy to total treatment duration of 24 months. Participants who after SL-IT (week 24) have a response (NAD or AD better) are eligible for randomization between the continuation arms "INDOMETHACIN" and "6-MP/MTX" (mercaptopurine and Methotrexate).

Ostatní jména:
  • Cytarabin, Ara-C

Stratum I

Stratum I

Ostatní jména:
  • Velban®
  • Vincaleukoblastin sulfát

Stratum I

Ostatní jména:
  • -Purinethol®
  • -6-MP

Indomethacin fixed dose given daily orally in two divided doses with gastric protection for total treatment duration of 24 months.

fixed dose weekly orally for total treatment duration of 24 months.

Experimentální: Stratum III

Salvage treatment for risk LCH To assess the efficacy of the combination 2-CdA/Ara-C (Cytosine Arabinoside and 2-chlorodeoxyadenosine) in MS-LCH (patients with risk organ involvement, who fail to respond to front-line (Stratum I) therapy.

The initial therapy consists of 2 courses of 2-CdA/Ara-C. Continuation of outlined treatment to be assessed at assigned intervals in each stratum.

Ostatní jména:
  • Leustatin®
  • 2-CdA
  • Kladribin®
Experimentální: Stratum IV

To determine the overall and disease free survival at 1 and 3 years after reduced intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT). Salvage treatment option for MS-LCH patients with risk organ involvement, who fail to respond to front-line therapy (Stratum I) OR to the salvage 2- CdA/Ara-C regimen (Stratum III).

Experimentální: Stratum V

Stratum V Monitoring and Treatment of isolated tumorous and neurodegenerative CNS-LCH

- Special regimens will be offered to patients with isolated tumorous CNS-LCH (repeated 2-CdA courses) and to patients with clinically manifested ND-CNS-LCH (+/- extracranial LCH manifestations). For the last group monotherapy with Ara-C courses or (Intravenous immunoglobulin)IVIG will be offered depending on physician's choice.

Ostatní jména:
  • Cytarabin, Ara-C
Ostatní jména:
  • Leustatin®
  • 2-CdA
  • Kladribin®
Ostatní jména:
  • IVIG
Experimentální: Stratum VI

Natural history and management of "other" SS-LCH not eligible for stratum I group 2.

  • Treatment Options- Management (mostly "wait & see" and topical treatment) is left to the discretion of the treating physician. All treatments and disease responses must be reported in the database. In the case of uncertainties please contact your National Coordinator.
  • Patients being followed on Stratum VI who have progression of disease to MSLCH, multifocal bone disease or CNS-risk bone lesions should be enrolled on Stratum I therapy.
  • Patients being followed on Stratum VI who develop isolated tumorous or neurodegenerative CNS-LCH should be enrolled on Stratum V.
Ostatní jména:
  • Cytarabin, Ara-C
Ostatní jména:
  • Leustatin®
  • 2-CdA
  • Kladribin®
Ostatní jména:
  • IVIG

Stratum I

Stratum I

Ostatní jména:
  • Velban®
  • Vincaleukoblastin sulfát

Stratum I

Ostatní jména:
  • -Purinethol®
  • -6-MP

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Patients with Reactivation Free Survival
Časové okno: 12 Months

Stratum I, II, VI

12 Months
Response Rate of Second Cycle
Časové okno: 9 weeks

Stratum III

9 weeks
Overall and disease free survival at 1 and 3 years after reduced intensity conditioning hematopoietic stem cell transplantation (RIC-HSCT)
Časové okno: 3 Years

Stratum IV

3 Years
The cumulative incidence of radiological and clinical neurodegeneration in patients with isolated tumorous CNS-LCH, DI, anterior pituitary dysfunction, and those with CNS-risk lesions
Časové okno: 2 Years

Stratum V

2 Years
The time interval and cumulative incidence of progression of radiological neurodegeneration to clinically manifested ND-CNS-LCH
Časové okno: 2 Years

Stratum V

2 Years
Cumulative incidence of specific Permanent Consequences e.g. diabetes insipidus (DI), growth hormone deficiency (GHD), neuropsychological impairment, etc.
Časové okno: 2 Years

From all treatment stratum via long-term follow up in Stratum VII

2 Years

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Počet účastníků se závažnými a nezávažnými nežádoucími příhodami
Časové okno: 2 roky
2 roky
Kumulativní výskyt reaktivací v rizikových orgánech
Časové okno: 2 roky
2 roky
Výskyt hematopoetického zotavení a dárcovského chimérismu v d+100 a 1 rok po RIC-HSCT
Časové okno: 2 roky
2 roky
Identifikujte možné rizikové faktory trvalých následků (PC)
Časové okno: 2 roky
2 roky
Overall Survival
Časové okno: 2 Years

Stratum I

2 Years
Incidence of Permanent Consequences
Časové okno: 2 Years

All Stratum

2 Years
Time to complete disease resolution
Časové okno: 2 Years

Stratum III

2 Years
Response rate to the combination of prednisone, vincristine and cytarabine
Časové okno: 2 years

Stratum II

2 years
The proportion of patients alive and free of disease without permanent consequences (e.g. diabetes insipidus, anterior pituitary dysfunction, radiological or clinical neurodegeneration)
Časové okno: 2 Years

Stratum II

2 Years
Percentage of treatment-related toxicities
Časové okno: 2 Years

Stratum II

2 Years
Reactivation rates after continuation treatment with Indomethacin vs. 6-MP/MTX.
Časové okno: 2 years

Stratum II

2 years
The type of subsequent intensive and/or maintenance therapy utilized
Časové okno: 2 Years

Stratum III

2 Years
Early and late mortality
Časové okno: 2 Years

Stratum II

2 Years
Early and late toxicity
Časové okno: 2 Years

Stratum III

2 Years
d+100 transplant related mortality
Časové okno: 2 Years

Stratum IV

2 Years
Record all occurrence of skin, GI or liver abnormalities fulfilling criteria of Grades II-IV acute GVHD
Časové okno: 2 Years

Stratum IV: Hematopoetic Stem Cell Transplantation for Risk LCH

2 Years
Percentage of Participants with incidence of chronic GVHD
Časové okno: 2 Years

Stratum IV

2 Years
Response Rate to ND-CNS-targeted therapy at 12 and 24 months after start of therapy
Časové okno: 2 years

Stratum V

2 years
Response of isolated tumorous CNS-LCH to 2-CDA
Časové okno: 2 Years

Stratum V

2 Years
Frequency of ND-CNS-LCH in patients with isolated tumorous CNS-LCH
Časové okno: 2 Years

Stratum V

2 Years
Methods of early identification of ND-CNS-LCH
Časové okno: 2 Years

Stratum V - Exploration of the value of neurochemistry, neurophysiology, and neuropsychology methods in early identification of ND-CNS-LCH and in assessing its severity, and comparison to MRI findings.

2 Years
Need for systemic therapy later during disease course
Časové okno: 2 Years

Stratum VI

2 Years

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Spolupracovníci

Vyšetřovatelé

  • Studijní židle: Milen Minkov, MD, Ph.D, Children's Cancer Research Institute / St. Anna Children's Hospital
  • Studijní židle: Carlos Rodriguez-Galindo, MD, North American Consortium for Histiocytosis

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

2. listopadu 2016

Primární dokončení (Odhadovaný)

1. listopadu 2031

Dokončení studie (Odhadovaný)

1. listopadu 2031

Termíny zápisu do studia

První předloženo

7. července 2014

První předloženo, které splnilo kritéria kontroly kvality

30. července 2014

První zveřejněno (Odhadovaný)

31. července 2014

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

10. listopadu 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

9. listopadu 2026

Naposledy ověřeno

1. listopadu 2026

Více informací

Termíny související s touto studií

Další identifikační čísla studie

  • 13-428
  • 2011-001699-20 (Číslo EudraCT)
  • 042011 (Jiný identifikátor: Children's Cancer Research Institute)

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .